China
Africa
Explore chapters and articles related to this topic
Histology and Pathology of the Human Neuromuscular Junction with a Description of the Clinical Features of the Myasthenic Syndromes
Published in Marc H. De Baets, Hans J.G.H. Oosterhuis, Myasthenia Gravis, 2019
F.G.I. Jennekens, H. Veldman, John Wokke
The snake venom alpha-bungarotoxin (BTX) binds in a highly specific and near irreversible fashion to the ACh binding site of the AChR and blocks neuromuscular transmission. Treatment with BTX induces denervation-like changes in the muscle fibers, comparable to the situation in BoA intoxication, but more severe in degree, as seen after nerve transection. The difference with BoA intoxication can be explained by incomplete blockage of spontaneous quantal and nonquantal ACh release in BoA, and complete blockage of the ACh effect by BTX.107 There can be little doubt that BTX induced transmission block results in sprouting.108 According to Pestronk and Drachman, however, BTX has an inhibitory effect on the sprouting response induced by BoA.109 The proposed explanation is that the signal eliciting sprouting is related to extrajunctional AChRs and that binding of BTX to these receptors interferes with the signal. The reported inhibitory effect of BTX on nerve sprouting so far lacks confirmation.
The Thymus and Immunotherapy, Reconstructive Vs. Stimulatory or Suppressive Conceptions
Published in Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein, Immunoregulatory Role of Thymus, 2019
Marek P. Dabrowski, Barbara K. Dabrowska-Bernstein
Antoantibodies present in MG patients, directed to “A” bands of striated muscles, cross-react with thymic epithelial cells.338 Isolation of nicotinic acetylcholine (ACh) receptors and labeling these structures with the snake venom alpha-bungarotoxin,339 prompted the progress in the understanding of the pathogenesis of MG. In the majority of MG patients, B cells penetrate the thymus and form typical germinal centers synthesizing polyclonal immunoglobulins and anti-ACh receptor antibodies. In these patients, therapeutic thymectomy results in decreased levels of peripheral anti-ACh R antibodies and in corresponding improvement of neuromuscular transmission.340 In the group of remaining MG patients (10 to 20%), with developed thymoma, no clinical benefit is observed after thymectomy, suggesting the “peripheralization” of autoantibody production.
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
Alpha-bungarotoxin is a POLYPEPTIDE which can bind irreversibly to NICOTINIC ACETYLCHOLINE RECEPTORS, where it acts as an ANTAGONIST. It has a powerful action at the NEUROMUSCULAR JUNCTION, which it blocks, leading to paralysis and death by asphyxiation. It has been extracted from the venom of the banded krait (Bungarus multicinctus), a very dangerous Taiwanese snake.
BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders
Published in Expert Opinion on Investigational Drugs, 2023
Elliot Hampsey, Adam Perkins, Allan H. Young
BNC210 is a negative modulator of the α7 nAChR (see figure 1). BNC210 inhibits α7 nAChR currents in human cell lines with IC50 values in the range of 1.2 to 3 mM. It appears to act as a negative allosteric modulator, as it is neither displaced by alpha-bungarotoxin binding (a neurotoxin that competitively binds to nAChRs), nor are its effects impacted by the concentration of acetylcholine. There are no published data concerning BNC210ʹs off-target (i.e. non-nicotinic) activity. Data published by Wise, Patrick, & Meyer et al. [21], & Perkins, A., Patrick, F., Wise, T., et al. [22], suggest that the response to BNC210 may be hormetic, as low-dose, but not high dose, BNC210 resulted in reduced anxiolytic behaviors and reductions in scores on self-reported state anxiety.
In vitro models of neuromuscular junctions and their potential for novel drug discovery and development
Published in Expert Opinion on Drug Discovery, 2020
Olaia F Vila, Yihuai Qu, Gordana Vunjak-Novakovic
Alpha-bungarotoxin (BTX), a 74-amino acid polypeptide purified from the venom of the snake Bungarus multicinctus originally found in Taiwan [74], is another postsynaptic blocker frequently used to validate NMJ models. Santhanam et al. showed a dose-response curve to BTX treatment in their microfluidic NMJ system [46] whereas Uzel et al., and Vila et al. showed its ability to irreversibly stop both spontaneous and light-induced contractions in their mouse [60] and human [62] optogenetic NMJ models.